Plasma biomarkers in carbon monoxide poisoning

Abstract

Objectives: The severity of acute carbon monoxide (CO) poisoning is often based on non-specific clinical criteria because there are no reliable laboratory markers. We hypothesized that a pattern of plasma protein values might objectively discern CO poisoning severity. This was a pilot study to evaluate protein profiles in plasma samples collected from patients at the time of initial hospital evaluation. The goal was to assess whether any values differed from age- and sex-matched controls using a commercially available plasma screening package.

Methods: Frozen samples from 63 suspected CO poisoning patients categorized based on clinical signs, symptoms, and blood carboxyhemoglobin level were analyzed along with 42 age- and sex-matched controls using Luminex-based technology to determine the concentration of 180 proteins.

Results: Significant differences from control values were found for 99 proteins in at least one of five CO poisoning groups. A complex pattern of elevations in acute phase reactants and proteins associated with inflammatory responses including chemokines/cytokines and interleukins, growth factors, hormones, and an array of auto-antibodies was found. Fourteen protein values were significantly different from control in all CO groups, including patients with nominal carboxyhemoglobin elevations and relatively brief intervals of exposure.

Conclusions: The data demonstrate the complexity of CO pathophysiology and support a view that exposure causes acute inflammatory events in humans. This pilot study has insufficient power to discern reliable differences among patients who develop neurological sequelae but future trials are warranted to determine whether plasma profiles predict mortality and morbidity risks of CO poisoning.

Fig. 1

Plasma acute phase reactants found to be significantly elevated in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control. Abbreviation is as follows: vWF, von Willebrand factor.

Fig. 2

Plasma chemokines and cytokines found to be significantly different from control in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control. Abbreviations are as follows: RANTES, regulated on activated, normal T expressed and secreted chemokine; Gro-α, growth-related oncogene; TRAIL-R3, tumor necrosis factor-related apoptosis-inducing ligand decoy receptor; ENA-78, epithelial cell-derived neutrophil-activating peptide 78; PARC, pulmonary and activation-regulated chemokine; MCP-1, monocyte chemoattractant protein-1; MDC, macrophage-derived chemokine.

Fig. 3

Plasma interleukin (IL) proteins found to be significantly different from control in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control.

Fig. 4

Additional plasma proteins associated with inflammatory responses found to be significantly different from control in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control. Abbreviations are as follows: MMP, metalloproteinase; IgA, immunoglobulin A; PAI-1, plasminogen activator inhibitor-1.

Fig. 5

Plasma growth factors found to be significantly different from control in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control. Abbreviations are as follows: HBEGF, heparin binding endothelial growth factor; IGF-1, insulin-like growth factor; PDGF, platelet-derived growth factor; EGF-R, endothelial growth factor receptor; FGF-basic, fibroblast growth factor-basic.

Fig. 6

Plasma hormones found to be significantly different from control in two or more of the CO patient groups. Mean values ± SE for control and each of the five CO patient groups are shown. *Values are significantly different from control.

Fig. 7

General plasma proteins found to be significantly different from control in two or more of the CO patient groups. Mean values for control and each of the five CO patient groups are shown. *Values are significantly different from control.